MULTIPLE TYPES OF TACHYKININ RECEPTOR MEDIATE A SLOW EXCITATION OF RAT SPINAL MOTONEURONS IN-VITRO

Using intracellular current clamp recording from motoneurones of the n eonatal rat spinal cord in vitro, the action of tachykinin receptor ag onists was investigated. Test drugs included the endogenously occurrin g neuropeptide substance P and synthetic compounds, such as substance P methylester (SPMeO), [beta Ala(8)]neurokinin A(4-10) ([Ala]NKA), [Me Phe(7)]neurokinin B ([MePhe]NKB) and senktide. SPMeO and [Ala]NKA were used as selective agonists at NK1 and NK2 receptors, respectively, wh ile [MePhe]NKB or senktide were employed to activate NK3 receptors. In control solution, all compounds produced sustained depolarization wit h increase in input resistance although at comparable levels of membra ne depolarization different patterns of motoneuronal firing were obser ved dependent on the type of agonist tested. In tetrodotoxin (TTX; 1 m u M) solution, the depolarization caused by substance P or SPMeO large ly persisted while in the majority of cells the effect of [Ala]NKA, [M ePhe]NKB or senktide was blocked. It is suggested that NK1 receptors p rimarily mediated the actions of substance P on spinal motoneurones an d that activation of NK2 or NK3 receptors, predominantly found on inte rneurones, induced motoneuronal depolarization with different firing p atterns.